Abstract
Collagen XVI belongs to the family of fibril-associated collagens with interrupted triple helices (FACIT). It is overexpressed during the progression of oral squamous cell carcinoma (OSCC). The present data show a strong collagen XVI-dependent induction of MMP9 and an increase in OSCC cell invasion. We found activated integrin-linked kinase (ILK) in a complex with kindlin-1 and activation of protein kinase B (PKB/Akt) to be responsible for MMP9 induction. Inhibition of the formation of focal adhesions reduced MMP9 expression. Moreover, collagen XVI overexpressing OSCC cell clones (COLXVI cell clones) transfected with vectors containing different MMP9 promoter fragments adjacent to a luciferase reporter revealed an increase in luciferase signal dependent on AP-1 binding sites. Deletion of the AP-1 binding site 98 bp upstream of the reported transcription start site and inhibition of AP-1 with Tanshinone IIA resulted in decreased MMP9 expression. The AP-1 subunit JunB showed differential expression between COLXVI cell clones and mock control cells. Additionally, mass spectrometric analysis of immunoprecipitates revealed that c-Fos interacted strongly with dyskerin in COLXVI cell clones compared to mock controls.
Highlights
Oral squamous cell carcinoma (OSCC) is by far the most common form of head and neck cancer [1]
The OSCC cell line PCI13, which is essentially devoid of endogenous collagen XVI expression, was stably transfected with the coding DNA sequence of full-length collagen XVI
That collagen XVI expression is up-regulated in glioblastoma [14] and its inhibition leads to reduced glioma invasiveness [16]
Summary
Oral squamous cell carcinoma (OSCC) is by far the most common form of head and neck cancer [1]. Its incidence has increased sharply over the last 10 years. Despite continued improvements in surgery, chemotherapy and radiation therapy, the 5-year survival rate is still only about 50% [2]. This is due to the fact that malignant oral keratinocytes show a fast invasion of cervical lymph nodes and spread quickly to distant sites [3]. Our understanding of the molecular factors responsible for the strong invasive, migratory and proliferative activity of OSCC cells is still incomplete. We present data that imply a critical role of collagen XVI in OSCC invasion
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
